A large-scale trial has found that apixaban, a new anticoagulant drug, is superior to the standard drug warfarin for preventing stroke and systemic embolism in patients with atrial fibrillation.
Moreover, the study found, use of apixaban results in substantially less bleeding and lower mortality.
The results were presented Aug. 28 by Duke University Medical Center researchers at the European Society of Cardiology in Paris and published simultaneously on the website of the New England Journal of Medicine.
“These are important findings because they show that, when compared to warfarin, [which is]a very effective treatment to prevent stroke, apixaban resulted in an additional 21% relative reduction in stroke or systemic embolism,” said Christopher B. Granger, MD, the study’s lead author and professor of medicine at Duke. “It also resulted in a 31% relative reduction in major bleeding, as well as an 11% relative reduction in overall mortality.”
The randomized, double-blind clinical trial known as ARISTOTLE recruited 18,201 patients with atrial fibrillation at 1,034 clinical sites in 39 countries, giving them either five milligrams twice daily of apixaban or warfarin for an average of 1.8 years.
Apixaban has several major practical advantages over warfarin in addition to the therapeutic benefits, said John Alexander, MD, a study co-author and Duke cardiologist. “It does not require monitoring and has few interactions with other medications or food. Apixaban was better tolerated than warfarin, with fewer discontinuations.”
The benefits of reducing stroke and lower rates of bleeding were consistent across all major subgroups — despite the heterogeneity that exists in the quality of warfarin use across the world, Alexander said.
The number of events prevented per 1,000 people, which indicate absolute risk reduction, was also impressive, he said. Apixaban prevented six patients from having a stroke, 15 patients from having major bleeding and eight patients from dying. The major effect on stroke prevention was on hemorrhagic stroke. Apixaban prevented four patients from having hemorrhagic stroke and two patients from having an ischemic or uncertain type of stroke.
Warfarin is a vitamin K antagonist that is well documented for its ability to prevent blood clots. Previous studies indicate that long-term use of warfarin in patients with atrial fibrillation and other stroke risk factors can reduce stroke by up to 70%. But only about half of patients who could benefit from warfarin actually do. Patients on warfarin must have regular blood tests to monitor and adjust the dose and avoid certain foods and medications that interfere with warfarin’s effect.
“There is an enormous unmet need for treatment of patients at risk for stroke associated with atrial fibrillation,” Granger said. “Only about half of patients who should be treated are being treated. The disparity exists because warfarin treatment has several limitations.”
Apixaban is an oral direct factor Xa inhibitor that showed promise last year when trial findings presented at the European Society of Cardiology showed apixaban patients were 54% less likely to have a stroke or blood clot than those who took aspirin. Apixaban and aspirin showed similar risks of major bleeding.
To read the study, visit http://bit.ly/oWSpnl.